tbuckley/cabot-search huggingface dataset:
Emergence, spread and characterisation of the SARS-CoV-2 variant B.1.640 circulating in France, October 2021 to February 2022
Authors: Gwenola Picard, Lucie Fournier, Anna Maisa, Claire Grolhier, Souhaila Chent, Caroline Huchet-Kervalla, Jeanne Sudour, Maël Pretet, Laurence Josset, Sylvie Behillil, Justine Schaeffer
Journal: Eurosurveillance (2023)

Background Successive epidemic waves of COVID-19 illustrated the potential of SARS-CoV-2 variants to reshape the pandemic. Detecting and characterising emerging variants is essential to evaluate their public health impact and guide implementation of adapted control measures. Aim To describe the detection of emerging variant, B.1.640, in France through genomic surveillance and present investigations performed to inform public health decisions. Methods Identification and monitoring of SARS-CoV-2 variant B.1.640 was achieved through the French genomic surveillance system, producing 1,009 sequences. Additional investigation of 272 B.1.640-infected cases was performed between October 2021 and January 2022 using a standardised questionnaire and comparing with Omicron variant-infected cases. Results B.1.640 was identified in early October 2021 in a school cluster in Bretagne, later spreading throughout France. B.1.640 was detected at low levels at the end of SARS-CoV-2 Delta variant’s dominance and progressively disappeared after the emergence of the Omicron (BA.1) variant. A high proportion of investigated B.1.640 cases were children aged under 14 (14%) and people over 60 (27%) years, because of large clusters in these age groups. B.1.640 cases reported previous SARS-CoV-2 infection (4%), anosmia (32%) and ageusia (34%), consistent with data on pre-Omicron SARS-CoV-2 variants. Eight percent of investigated B.1.640 cases were hospitalised, with an overrepresentation of individuals aged over 60 years and with risk factors. Conclusion Even though B.1.640 did not outcompete the Delta variant, its importation and continuous low-level spread raised concerns regarding its public health impact. The investigations informed public health decisions during the time that B.1.640 was circulating.
Error in Supplement
Journal: JAMA Oncology (2023)

Alison M. Schram, MD; Nicoletta Colombo, MD, PhD; Edward Arrowsmith, MD; Vivek Narayan, MD, MS; Kan Yonemori, MD; Giovanni Scambia, MD; Amelia Zelnak, MD, MSc; Todd M. Bauer, MD; Ning Jin, MD; Susanna V. Ulahannan, MD, MMEd; Marco Colleoni, MD; Philippe Aftimos, MD; Mark T. A. Donoghue, MD; Ezra Rosen, MD, PhD; Vasilisa A. Rudneva, MD; Melinda L. Telli, MD; Susan M. Domchek, MD; Matthew D. Galsky, MD; Margaret Hoyle, BSc; Colombe Chappey, PhD; Ross Stewart, PhD; John A. Blake-Haskins, PharmD; Timothy A. Yap, MBBS, PhD
Pulmonary Function Prediction Equations—Clinical Ramifications of a Universal Standard
Authors: Adam Gaffney
Journal: JAMA Network Open (2023)

Alexander T. Moffett, MD; Cole Bowerman, MS; Sanja Stanojevic, PhD; Nwamaka D. Eneanya, MD; Scott D. Halpern, MD, PhD; Gary E. Weissman, MD
Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma
Authors: Lili Mao, Bin Lian, Caili Li, Xue Bai, Li Zhou, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Xuan Wang, Bixia Tang, Xieqiao Yan, Siming Li, Yan Kong, Jie Dai, Xiaoting Wei, Juan Li, Rong Duan, Huayan Xu, Xiaowen Wu, Yue Yang, Fengzhuo Cheng, Cheng Zhang, Fangzhou Xia, Zheng Pang, Jun Guo, Lu Si
Journal: JAMA Oncology (2023)

Acral melanoma, known for low tumor mutation burden, responds poorly to immunotherapy. A standard therapy is still lacking.
Update on Adipose Tissue and Cancer
Authors: Kristy A Brown, Philipp E Scherer
Journal: Endocrine Reviews (2023)

Adipose tissue is the largest endocrine organ and an accepted contributor to overall energy homeostasis. There is strong evidence linking increased adiposity to the development of 13 types of cancer. With increased adiposity comes metabolic dysfunction and insulin resistance, and increased systemic insulin and glucose support the growth of many cancers, including those of the colon and endometrium. There is also an important direct crosstalk between adipose tissue and various organs. For instance, the healthy development and function of the mammary gland, as well as the development, growth, and progression of breast cancer, are heavily impacted by the breast adipose tissue in which breast epithelial cells are embedded. Cells of the adipose tissue are responsive to external stimuli, including overfeeding, leading to remodeling and important changes in the secretion of factors known to drive the development and growth of cancers. Loss of factors like adiponectin and increased production of leptin, endotrophin, steroid hormones, and inflammatory mediators have been determined to be important mediators of the obesity-cancer link. Obesity is also associated with a structural remodeling of the adipose tissue, including increased localized fibrosis and disrupted angiogenesis that contribute to the development and progression of cancers. Furthermore, tumor cells feed off the adipose tissue, where increased lipolysis within adipocytes leads to the release of fatty acids and stromal cell aerobic glycolysis leading to the increased production of lactate. Both have been hypothesized to support the higher energetic demands of cancer cells. Here, we aim to provide an update on the state of the literature revolving around the role of the adipose tissue in cancer initiation and progression.
A genomic score to predict local control among patients with brain metastases managed with radiation
Authors: Nayan Lamba, Daniel N Cagney, Paul J Catalano, Dewey Kim, Hesham Elhalawani, Daphne A Haas-Kogan, Patrick Y Wen, Nikhil Wagle, Ayal A Aizer
Journal: Neuro-Oncology (2023)

Clinical predictors of local recurrence following radiation among patients with brain metastases (BrM) provide limited explanatory power. We developed a DNA-based signature of radiotherapeutic efficacy among patients with BrM to better characterize recurrence risk.
Assessing the robustness of COVID-19 vaccine efficacy trials: systematic review and meta-analysis, January 2023
Authors: Thi Ngoc Anh Hoang, Ha-Linh Quach, Van Ngoc Hoang, Van Thien Tran, Quang Thai Pham, Florian Vogt
Journal: Eurosurveillance (2023)

Background Vaccines play a crucial role in the response to COVID-19 and their efficacy is thus of great importance. Aim To assess the robustness of COVID-19 vaccine efficacy (VE) trial results using the fragility index (FI) and fragility quotient (FQ) methodology. Methods We conducted a Cochrane and PRISMA-compliant systematic review and meta-analysis of COVID-19 VE trials published worldwide until 22 January 2023. We calculated the FI and FQ for all included studies and assessed their associations with selected trial characteristics using Wilcoxon rank sum tests and Kruskal–Wallis H tests. Spearman correlation coefficients and scatter plots were used to quantify the strength of correlation of FIs and FQs with trial characteristics. Results Of 6,032 screened records, we included 40 trials with 54 primary outcomes, comprising 909,404 participants with a median sample size per outcome of 13,993 (interquartile range (IQR): 8,534–25,519). The median FI and FQ was 62 (IQR: 22–123) and 0.50% (IQR: 0.24–0.92), respectively. FIs were positively associated with sample size (p &lt; 0.001), and FQs were positively associated with type of blinding (p = 0.023). The Spearman correlation coefficient for FI with sample size was moderately strong (0.607), and weakly positive for FI and FQ with VE (0.138 and 0.161, respectively). Conclusions This was the largest study on trial robustness to date. Robustness of COVID-19 VE trials increased with sample size and varied considerably across several other important trial characteristics. The FI and FQ are valuable complementary parameters for the interpretation of trial results and should be reported alongside established trial outcome measures.
Authors' Reply: A Specific Target BP in Chronic Kidney Disease Remains Unclear
Authors: Elaine Ku, Charles E. McCulloch, Mark J. Sarnak
Journal: Journal of the American Society of Nephrology (2023)

1Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 2Department of Medicine, Tufts Medical Center, Boston, Massachusetts Correspondence: Elaine Ku, 500 Parnassus Avenue MBU-E 414, San Francisco, CA 94131. Email: [email protected] See letter to the editor, "A Specific Target BP in Chronic Kidney Disease Remains Unclear," on pages 1121–1122, and original article "Intensive BP Control in Patients with CKD and Risk for Adverse Outcomes," in Vol. 34, Iss. 3, on pages 385–393.
Evidence Base for Health Care Strategies to Protect Vulnerable Patients During the COVID-19 Pandemic—Reply
Authors: Michael Hoerger, James Gerhart, Maria C. Swartz
Journal: JAMA Oncology (2023)

][3] Accordingly, in our Editorial, 1 we encouraged cancer centers to provide more comprehensive pandemic support, suggested 10 evidence-based recommendations, and offered volunteer assistance.We appreciate Haslam and Prasad's comments on this evidence base.Foremost, our recommendations 1 focused on patient education about COVID-19, transmission, and mitigation.Haslam and Prasad questioned the importance of educational interventions.Patient education has been the cornerstone of patient-centered oncology for more than 50 years, 4 the foundation of several journals, and an umbrella intervention found to be efficacious in meta-analyses.Education and outreach about high-quality (N95) masking, for example, can be highly successful. 5Second, Haslam and Prasad asked about N95 efficacy.The National Institute for Occupational Safety and Health establishes and monitors N95 efficacy.The approval process demands years, involves testing N95s to ensure efficacy in blocking greater than 95% of particles that are substantially smaller than virus-laden respiratory aerosol particles, and includes product audits annually and site audits every 2 years to monitor sustained efficacy, inspect materials, and validate quality-control procedures.Third, Haslam and Prasad expressed curiosity about HEPA.HEPA filters undergo rigorous efficacy validation and monitoring tests to ensure they remove more than 99.97% of the small and most-penetrating 0.3micron airborne particles, reducing airborne doses of dust, dirt, pollen, smoke, bacteria, and virus-laden aerosol particles.We were pleased that Haslam and Prasad did not contest the importance of vaccines, testing, treatment, local COVID-19cautious resources, and problem-solving support.We had a difference of opinion on several conceptual points.In our opinion, Haslem and Prasad cited low-rigor studies that were not focused on high-quality masks.Efficacy data come from the methodologies noted above, not later-stage T3 comparative effectiveness trials, which have limitations related to low adherence, low fidelity, and low monitoring.Second, SARS-CoV-2 poses cumulative harm from reinfections. 1,6n infection or a reinfection remains a notable concern in a population that may have a limited treatment window 2 and limited life span.Third, reasonable mitigation can enhance rather than detract from social well-being by allowing friends and family to visit more safely with less concern toward disrupting a loved one's oncology care.Several types of mitigation require little to no cost.In sum, people with cancer are among the most vulnerable to severe outcomes associated with COVID-19.Health care systems are encouraged to develop comprehensive supports to reduce the risks of COVID-19 among this vulnerable population.
Association of Prescription Co-payment With Adherence to Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Therapies in Patients With Heart Failure and Diabetes
Authors: Utibe R. Essien, Balvindar Singh, Gretchen Swabe, Amber E. Johnson, Lauren A. Eberly, Rishi K. Wadhera, Khadijah Breathett, Muthiah Vaduganathan, Jared W. Magnani
Journal: JAMA Network Open (2023)

Importance Type 2 diabetes (T2D) and heart failure (HF) prevalence are rising in the US. Although glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes for these conditions, high out-of-pocket costs may be associated with reduced medication adherence. Objective To compare 1-year adherence to GLP1-RA and SGLT2i therapies by prescription co-payment level in individuals with T2D and/or HF. Design, Setting, and Participants This retrospective cohort study used deidentified data from Optum Insight’s Clinformatics Data Mart Database of enrollees with commercial and Medicare health insurance plans. Individuals aged 18 years or older with T2D and/or HF who had a prescription claim for a GLP1-RA or SLGT2i from January 1, 2014, to September 30, 2020, were included. Exposures Prescription co-payment, categorized as low (&amp;amp;lt;$10), medium ($10 to&amp;amp;lt;$50), and high (≥$50). Main Outcomes and Measures The primary outcome was medication adherence, defined as a proportion of days covered (PDC) of 80% or greater at 1 year. Logistic regression models were used to examine the association between co-payment and adherence, adjusting for patient demographics, medical comorbidities, and socioeconomic factors. Results A total of 94 610 individuals (mean [SD] age, 61.8 [11.4] years; 51 226 [54.1%] male) were prescribed GLP1-RA or SGLT2i therapy. Overall, 39 149 individuals had a claim for a GLP1-RA, of whom 25 557 (65.3%) had a PDC of 80% or greater at 1 year. In fully adjusted models, individuals with a medium (adjusted odds ratio [AOR], 0.62; 95% CI, 0.58-0.67) or high (AOR, 0.47; 95% CI, 0.44-0.51) co-payment were less likely to have a PDC of 80% or greater with a GLP1-RA compared with those with a low co-payment. Overall, 51 072 individuals had a claim for an SGLT2i, of whom 37 339 (73.1%) had a PDC of 80% or greater at 1 year. Individuals with a medium (AOR, 0.67; 95% CI, 0.63-0.72) or high (AOR, 0.68; 95% CI, 0.63-0.72) co-payment were less likely to have a PDC of 80% or greater with an SGLT2i compared with those with a low co-payment. Conclusions and Relevance In this cohort study of individuals with T2D and/or HF, 1-year adherence to GLP1-RA or SGLT2i therapies was highest among individuals with a low co-payment. Improving adherence to guideline-based therapies may require interventions that reduce out-of-pocket prescription costs.
Vibratory and Cooling Detection Thresholds Compared With Other Tests in Diagnosing and Staging Diabetic Neuropathy
Authors: Peter James Dyck, Wilfred Bushek, Eileen M Spring, Jeannine L Karnes, William J Litchy, Peter C O'Brien, F John Service
Journal: Diabetes Care (1987)

Increasingly more tests are being used to detect and characterize diabetic polyneuropathy, but their value in setting minimal criteria for the diagnosis of neuropathy and for staging severity remains inadequately studied. In 180 diabetics, we compared the percentage of patients with test abnormalities and associations among test results, evaluating neuropathic symptoms [neuropathy symptom score (NSS) and neuropathy scale of neuropathy symptom profile (NNSP)], deficits [neurologic disability score (NDS) and vibratory (VDT) and cooling (CDT) detection thresholds], or nerve dysfunction [nerve conduction (NC)]. The percentage of patients that were abnormal varied considerably depending on criteria for abnormality and the tests used. Abnormality (≥ 3 SD of 1 or more parameters) of NC of one or more of four nerves occurred in 80%, of two or more in 69%, of three or more in 46%, and of four in 21%. Similarly, for other tests, the rate of abnormality decreased with use of increasingly stringent criteria. Setting the criteria for abnormal NC at abnormality of two or more nerves, NSS at ≥ 1, NDS at &amp;gt; 6, NNSP at ≥ 97.5th percentile, and at ≥ 95th percentile for the other tests, NC was abnormal in 69%, NSS in 54%, NDS in 48%, NNSP in 47%, VDT in 44%, and CDT in 35%. Abnormality of any two or more of the six tests evaluated occurred in 64% of patients. We estimated that at least 16% of patients without abnormal NC (&amp;lt;2 abnormal nerves) had other findings indicative of neuropathy. By regression analysis, results of one test were in almost all cases associated with those of another test, but the association was not close enough to be predictive. Therefore, although NC provides objective and repeatable results, symptoms and deficits must be measured independently. Assuming no differences between groups of patients, the standardized and validated test (NNSP, VDT, or CDT) should provide the same results at different medical centers. By contrast, the results of NSS or NDS tests, with less standardized approaches and based on the judgment of physicians, might not provide the same results at different medical centers. Tests such as the ones described here may be used to define minimal criteria for the diagnosis of polyneuropathy and for staging its severity.
Li–Mg–Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration
Authors: Yiting Sun, Hongjian Zhang, Yu Zhang, Zheqi Liu, Dongming He, Wanlin Xu, Siyi Li, Chenping Zhang, Zhen Zhang
Journal: Bioactive Materials (2023)

Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local immune response. However, little is known on whether inorganic bioceramics can have potential for enhancing peripheral nerve regeneration and what are the mechanisms underlying their actions. Here, the inorganic lithium-magnesium-silicon (Li-Mg-Si, LMS) bioceramics containing scaffolds are fabricated and characterized. The LMS-containing scaffolds had no cytotoxicity against rat Schwann cells (SCs), but promoted their migration and differentiation towards a remyelination state by up-regulating the expression of neurotrophic factors in a β-catenin-dependent manner. Furthermore, using single cell-sequencing, we showed that LMS-containing scaffolds promoted macrophage polarization towards the pro-regenerative M2-like cells, which subsequently facilitated the migration and differentiation of SCs. Moreover, implantation with the LMS-containing nerve guidance conduits (NGCs) increased the frequency of M2-like macrophage infiltration and enhanced nerve regeneration and motor functional recovery in a rat model of sciatic nerve injury. Collectively, these findings indicated that the inorganic LMS bioceramics offered a potential strategy for enhancing peripheral nerve regeneration by modulating the immune microenvironment and promoting SCs remyelination.
The effects of cash transfer programmes on HIV/AIDS prevention and care outcomes: a systematic review and meta-analysis of intervention studies
Authors: Nathalia Sernizon Guimarães, Laio Magno, Adelzon Assis de Paula, Miriam Silliman, Rodrigo Volmir Rezende Anderle, Davide Rasella, James Macinko, Luís Eugênio de Souza, Inês Dourado
Journal: The Lancet HIV (2023)
Thinking, both global and local
Authors: Robert Stirrups
Journal: The Lancet Neurology (2023)

For many people, consciousness is the biggest mystery of the universe; the hard problem of how subjective experience can arise has been the source of philosophical speculation for centuries and psychological research for decades. Even setting aside esoteric concepts such as the soul or panpsychism, there are many conflicting views on the issue. Within neuroscience, two main schools of thought prevail: globalism and localism. However, neither perspective adequately explains the current experimental evidence, and in In Consciousness We Trust: The Cognitive Neuroscience of Subjective Experience, Hakwan Lau makes the case for a synthesis.
Integrated Piezoelectric/Conductive Composite Cryogel Creates Electroactive Microenvironment for Enhanced Bone Regeneration
Authors: Tianyi Zheng, Yanyun Pang, Daixing Zhang, Yue Wang, Xu Zhang, Huijie Leng, Yingjie Yu, Xiaoping Yang, Qing Cai
Journal: Advanced Healthcare Materials (2023)

Natural bone tissue possesses inherent electrophysiological characteristics, displaying conductivity and piezoelectricity simultaneously; hence, the reconstruction of local electrical microenvironment at defect site provides an effective strategy to enhance osteogenesis. Herein, a composite cryogel-type scaffold (referred to as Gel-PD-CMBT) is developed for bone regeneration, utilizing gelatin (Gel) in combination with a conductive poly(ethylene dioxythiophene)/polystyrene sulfonate matrix and Ca/Mn co-doped barium titanate (CMBT) nanofibers as the piezoelectric filler. The incorporation of these components results in the formation of an integrated piezoelectric/conductive network within the scaffold, facilitating charge migration and yielding a conductivity of 0.59 S cm-1 . This conductive scaffold creates a promising electroactive microenvironment, which is capable of up-regulating biological responses. Furthermore, the interconnected porous structure of the Gel-PD-CMBT scaffold not only provides mechanical stability but also offered ample space for cellular and tissue ingrowth. This Gel-PD-CMBT scaffold demonstrates a greater capacity to promote cellular osteogenic differentiation in vitro and neo-bone formation in vivo. In summary, the Gel-PD-CMBT scaffold, with its integrated piezoelectricity and conductivity, effectively restores the local electroactive microenvironment, offering an ideal platform for the regeneration of electrophysiological bone tissue.
Host test based on tumor necrosis factor-related apoptosis-inducing ligand, interferon gamma-induced protein-10 and C-reactive protein for differentiating bacterial and viral respiratory tract infections in adults: diagnostic accuracy study
Authors: Salim Halabi, Shachaf Shiber, Meital Paz, Tanya M. Gottlieb, Eran Barash, Roy Navon, Tahel Ilan-Ber, Liran Shani, Neta Petersiel, Mordechai Grupper, Einav Simon, Daniel Kirshner, Daniel Haber, Michal Stein, Yasmin Maor, Claire Guetta, Ynon Lishtzinsky, Shirly Yanai, Michael J. Drescher, Kfir Oved, Eran Eden, Ami Neuberger, Mical Paul
Journal: Clinical Microbiology and Infection (2023)

To assess the performance of a test (called BV), integrating the blood levels of three immune proteins into a score, to differentiate bacterial from viral infection among adults with suspected lower respiratory tract infection (LRTI).Prospective diagnostic accuracy study, enrolling febrile adults >18 years with LRTI signs or symptoms for less than 7 days presenting to several hospitals' emergency departments in Israel. The main exclusion criterion was immunodeficiency. Reference standard diagnosis (bacterial/viral/indeterminate) was based on three experts independently reviewing comprehensive patient data including follow-up data. BV generated three results: viral infection or other nonbacterial condition (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65) and bacterial infection including co-infection (65 < score ≤ 100). BV performance was assessed against the reference standard with indeterminate reference standard and equivocal BV cases removed.Of 490 enrolled patients, 415 met eligibility criteria (median age 56 years, interquartile range 35). The reference standard classified 104 patients as bacterial, 210 as viral and 101 as indeterminate. BV was equivocal in 9.6% (30/314). Excluding indeterminate reference standard diagnoses and equivocal BV results, BV's sensitivity for bacterial infection was 98.1% (101/103; 95% confidence interval 95.4-100), specificity 88.4% (160/181; 83.7-93.1) and negative predictive value 98.8% (160/162; 97.1-100).BV exhibited high diagnostic performance for febrile adults with suspected LRTI among patients with reference standard diagnoses of bacterial or viral LRTI.